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Sci. Signal., 20 April 2010
Vol. 3, Issue 118, p. ec116
[DOI: 10.1126/scisignal.3118ec116]

EDITORS' CHOICE

Cell Biology Translation Under Stress

Wei Wong

Science Signaling, AAAS, Washington, DC 20005, USA

The transcription factor p53 induces cell cycle arrest in G1 or G2 in response to cellular stress. During cellular stress, initiation of mRNA translation through cap-dependent mechanisms is blocked and must instead occur through cap-independent means. p53/47 is an alternative splice isoform of p53 lacking the first 39 amino acids that can be produced through cap-independent translation initiation, whereas full-length p53 appears to be primarily produced by cap-dependent mechanisms. Bourougaa et al. investigated the role of mRNA translation of full-length p53 and p53/47 during endoplasmic reticulum (ER) stress. Thapsigargin treatment (to induce ER stress) of cells transfected with small interfering RNA (siRNA) directed against p53 decreased the number of cells arrested in G2 compared to cells transfected with control siRNA. Expression of both full-length (p53FL) and p53/47 isoforms arrested cells in G1, whereas selective expression of the p53/47 isoform arrested cells in G2; both effects were increased in thapsigargin-treated cells. p53/47 expression increased 14-3-3{sigma} mRNA abundance and increased occupancy of the p53 response element in the 14-3-3{sigma} promoter. In addition, transfection of siRNA directed against 14-3-3{sigma} decreased the number of p53/47-expressing cells arrested in G2. Thapsigargin exposure increased the mRNA abundance of p53/47, but not that of p53FL, an effect that was reduced by expression of a dominant-negative mutant of the ER stress sensor PERK (RNA-activated protein kinase–like ER-localized eIF2{alpha} kinase). Expression of the PERK mutant also reduced p53/47-mediated increases in 14-3-3{sigma} mRNA abundance and G2 arrest in thapsigargin-treated cells. Transcriptionally active p53 binds to DNA as a tetramer, and ER stress induced by thapsigargin increased the tetramerization of p53/47 and decreased that of p53FL. Selective expression of p53/47, but not of p53FL, increased ER stress–induced increases in apoptosis and in the mRNA abundance of PUMA, which encodes a proapoptotic factor. Thus, these results define a specific role for the p53/47 isoform in inducing G2 arrest in ER stress responses.

K. Bourougaa, N. Naski, C. Boularan, C. Mlynarczyk, M. M. Candeias, S. Marullo, R. Fåhraeus, Endoplasmic reticulum stress induces G2 cell-cycle arrest via mRNA translation of the p53 isoform p53/47. Mol. Cell 38, 78–88 (2010). [PubMed]

Citation: W. Wong, Translation Under Stress. Sci. Signal. 3, ec116 (2010).

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